MicroRNA 155 modulates megakaryopoiesis at progenitor and  precursor level by targeting Ets-1 and Meis1 transcription  factors.
MicroRNAs (miRNAs) control basic biological functions and are emerging as key regulators of haematopoiesis. This study focused on the functional role of MIRN155 on megakaryocytic (MK) differentiation of human cord blood CD34+ haematopoietic progenitor cells (HPCs). MIRN155, abundantly expressed in early HPCs, decreases sharply during MK differentiation. Functional studies showed that enforced expression of MIRN155 impairs proliferation and differentiation of MK cells. Furthermore, HPCs transfected with MIRN155 showed a significant reduction of their MK clonogenic capacity, suggesting that down-modulation of this miRNA favours MK progenitor differentiation. Consistent with this observation, MIRN155 downregulates, by directly binding to their 3'-UTR, the expression of Ets-1 and Meis1, two transcription factors with well-known functions in MK cells. These results show that the decline of MIRN155 is required for MK proliferation and differentiation at progenitors and precursors level and indicate that sustained expression of MIRN155 inhibits megakaryopoiesis.
Romania
Paolo
P
Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Lulli
Valentina
V
Pelosi
Elvira
E
Biffoni
Mauro
M
Peschle
Cesare
C
Marziali
Giovanna
G
D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology*; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D034061:Thrombopoiesis / Q000235:genetics* / Q000502:physiology; D014162:Transfection
C494041:ETS1 protein, human; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger